The pharmacology of dopamine receptors was investigated with biochemical techniques during FY 85. The 'two dopamine receptor' hypothesis (which was formulated within ETB during 1979) provided the basis for these investigations. The BI Section developed an iodinated ligand which selectively interacts with the D-1 receptor. The development of this ligand permitted binding studies of the D-1 receptor to be performed with minute samples of tissue. The ligand permits the affinity of drugs for the D-1 receptor to be directly demonstrated (the binding studies provide only indirect evidence for the efficacy of drugs towards the receptor). The ligand also permits biochemical studies of the dopamine recognition site of the D-1 receptor to be undertaken. During FY 85, the D-2 dopamine receptor was also investigated. The process of 'desensitization' of the D-2 receptor in the intermediate lobe of the rat pituitary gland was investigated with an iodinated derivative of spiroperidol. Exposure of intermediate lobe tissue to D-2 agonists causes a diminution in the affinity of the receptor for antagonists and agonists. The drug-induced alterations in the properties of the binding site are correlated with drug-induced changes in the properties of the adenylate cyclase (which were described within the BI Section during FY 84). The role of cAMP in the process of calcium-dependent hormone secretion was also investigated during FY 85. Studies were completed with the prolactin-secreting 7315c tumor cell. In this tumor, it was possible to demonstrate potentiation by forskolin, a non-specific activator of adenylate cyclase, of prolactin release from the cells induced by either potassium or ionomycin. Forskolin did not affect the rise in cytosolic calcium produced by either secretagogue.